Stephen J. McGeady

Hyposmia in allergic rhinitis

BACKGROUND The association between nasal allergy and loss or diminution of smell is frequently alluded to in the literature; however, neither the true prevalence of hyposmia in individuals with allergic rhinitis nor its bases have been established. METHODS We assessed olfactory threshold for phenylethyl alcohol in 91 patients with symptoms of allergic rhinitis and 80 nonatopic control subjects. To determine the degree to which nasal congestion contributes to hyposmia in allergic rhinitis, total nasal resistance was measured in 64 of the patients and 72 of the control subjects. RESULTS Olfactory thresholds were significantly higher in allergic patients than in control subjects (p < 0.001), with 23.1% of the patients demonstrating a clinically significant smell loss (defined as threshold at or above the 2.5th percentile of control values). Although nasal resistance was significantly higher among patients than among controls (p < 0.001), it was not related to olfactory threshold in either group. Clinical or radiographic evidence of sinusitis or nasal polyps or both in allergy patients was found to be significantly associated with hyposmia (p < 0.006). CONCLUSIONS The observed prevalence of hyposmia among patients with allergic rhinitis suggests that this is a major etiologic factor contributing to smell disorders. Sinusitis or nasal polyps or both may underlie many cases of allergy-related hyposmia.

Diagnosis and treatment of gastroesophageal reflux in children and adolescents with severe asthma.

BACKGROUND The ability of gastroesophageal reflux disease to provoke asthma is controversial. Recent reports have suggested that reflux to the proximal esophagus may be especially likely to aggravate asthma, but the prevalence of proximal reflux in children and adolescents is poorly documented. It is also unclear how sensitive and specific the commonly used tests of reflux, barium swallow, and scintiscan are compared with pH probe studies in young patients. There is limited information on the effectiveness of the combination of H2 blockers and prokinetic agents in controlling reflux in children. OBJECTIVE There were three objectives in this study: (1) to determine the prevalence of both proximal and distal gastroesophageal reflux in asthmatic children and adolescents; (2) to determine the sensitivity, specificity, positive and negative predictive values of barium swallow and scintiscan studies; and (3) to determine the effectiveness of standard antireflux pharmacotherapy. METHODS A 24-hour, 2-channel pH probe study was carried out in 79 asthmatic children aged 2 to 17 years. The prevalence of abnormal proximal and distal gastroesophageal reflux was calculated from the findings. In 63 of these patients, barium swallow and Technetium99 scintiscan were carried out and the findings used to calculate the sensitivity, specificity, positive and negative predictive value of these studies relative to pH probe. In 11 subjects a follow-up, 24-hour pH probe was carried out after at least 3 weeks of therapy with an H2 blocker and prokinetic agent to determine the efficacy of therapy. RESULTS There was abnormal proximal esophageal reflux in 64.5% of subjects and abnormal distal reflux in 73.4%. The sensitivity, specificity, positive and negative predictive values of barium swallow were 46.1%, 83.3%, 82% and 51%, respectively. Those of scintiscan were 15%, 72.7%, 50% and 32%, respectively. Of 11 subjects studied by repeat pH probe, 10 had persistent abnormal reflux. CONCLUSION Abnormal reflux into the proximal esophagus occurs in the majority of asthmatic children with difficult-to-control disease. The barium swallow and scintiscan compare poorly with pH probe in diagnosing reflux. Treatment of reflux with recommended does of H2 blockers and prokinetic agents has a high failure rate, and follow-up studies are essential.

Posterior subcapsular cataracts in steroid-requiring asthmatic children

Slit-lamp examinations were performed on 24 children and adolescents with severe asthma, all of whom had received steroids for at least 365 days. Posterior subcapsular cataracts (PSCC) were detected in 7 (29.1%). None of the patients had been treated with beclomethasone. All 7 of the patients with PSCC were in the subgroup of 14 patients who had been on the highest doses of corticosteroid, 10 mg or more per day, for the longest period of time. The 7 children with PSCC were all below the fifth percentile for height and had fallen away from their normal growth curve. Of the 17 children in whom PSCC were not detected, only 1 was below the fifth percentile for height. It would seem from our results that the steroid-requiring asthmatic who is growth-suppressed is at an increased risk for developing PSCC. We have documented the reversal of PSCC in 2 children. Both of these children had been placed on beclomethasone, which allowed for the discontinuation of daily prednisone in one case and a reduction to less than 10 mg per day of prednisone in the other. The reversal occurred within 6 months of starting on beclomethasone.

Infants Presenting with Recurrent Infections and Low Immunoglobulins: Characteristics and Analysis of Normalization

To better characterize infants presenting with diminished immunoglobulin levels and intact antibody formation, we present 49 such infants, correlating presenting characteristics with history and time to immunoglobulin normalization. Term infants with the following characteristics were included: 1) one or more immunoglobulin classes > 2SD below mean, 2) protective antibody titer to tetanus and diphtheria, 3) intact cellular immunity, 4) no features of other syndromes. The children were 69.4% male and had recurrent otitis media (77.6%), wheezing (61.2%), and atopy (26.5%). Diminished IgA (95.9%) was most common, but 65.3% had multiple isotypes diminished. During follow-up, 25/49 (51%) normalized immunoglobulins, of whom 80% were male; only 48% normalized in infancy. Female immunoglobulin normalization was significantly delayed (p < .001). No deaths or serious infections occurred. This phenotype is predominantly seen in male infants with otitis media and wheezing. Female infants have significantly delayed immunoglobulin normalization. Transient hypogammaglobulinemia of infancy can be diagnosed only retrospectively.

SCH 434: A new antihistamine/decongestant for seasonal allergic rhinitis☆

In a double-blind, multicenter study, we compared the effects of SCH 434 (Claritin-D; Schering Corp., Kenilworth, N.J.), a new sustained-release, combination antihistamine/decongestant medication, with the effects of its individual components and placebo in 435 patients with seasonal allergic rhinitis. SCH 434 contains 5 mg of loratadine, a nonsedating antihistamine, and 120 mg of pseudoephedrine as the decongestant component. Administered twice daily in this study, SCH 434 effected a 50% decrease in total symptom scores at day 4 and was significantly (p less than or equal to 0.03) more effective than the components alone or the placebo. Loratadine or pseudoephedrine alone, with 43% and 33% decline in symptom scores, respectively, also was more effective than placebo (p less than 0.05). As expected, pseudoephedrine alone was more effective than loratadine (p less than 0.01) in relieving nasal stuffiness; SCH 434 was more effective (p less than or equal to 0.01) than placebo and loratadine in relieving nasal stuffiness. All treatments were safe and well tolerated, although insomnia and dry mouth were noted in a significant number of patients who received either SCH 434 or pseudoephedrine. No serious side effects were noted. The incidence of sedation did not differ significantly among the four treatment groups. We conclude that SCH 434 is a safe and effective treatment for symptoms of seasonal allergic rhinitis. The combination drug (SCH 434) was better than its components for some, but not all, symptoms.

Hereditary angioedema with recurrent abdominal pain and ascites

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Lymphocyte subpopulations of atopic children and the effect of therapy upon them

Recent reports note decreased T cell function in association with certain atopic conditions in man. This study was performed to determine whether numbers of circulating T cells are decreased in atopic children and adolescents in comparison with nonatopic age-matched control subjects. The subjects were not selected on the basis of a particular atopic diagnosis, but relatively more had allergic rhinitis and/or asthma (52) than had atopic eczema (7). Numbers of circulating T cells were not found to be significantly different in allergic children aged 2 to 10 yr than in control subjects. Atopic children and adolescents over age 10 yr had significantly fewer T cells in relative percentages (p less than 0.05), but when absolute numbers were considered significance was lost. Atopic children aged 2 to 10 years had significantly more B cells in both relative percentages and absolute numbers than did control subjects (p less than 0.02 and p less than 0.05, respectively). When those subjects treated with corticosteroids were separated from the total atopic group, there were no significant differences between the atopic and control subjects. The effects of corticosteroids, bronchodilators, antihistamines, and immunotherapy were considered and could be shown to produce no consistent effect on lymphocyte subpopulations.

Lactic acidosis and status asthmaticus: how common in pediatrics?

BACKGROUND Lactic acidosis is a well described phenomenon in adult patients with severe asthma. However, this entity is rarely reported in children with status asthmaticus. OBJECTIVE To report our experience in a 13-year-old girl who developed lactic acidosis as a complication of status asthmaticus and to investigate the prevalence of this complication of severe asthma. We sought to determine the frequency of lactic acidosis in such patients and to review etiologies of lactic acidosis. METHODS 1) Observations on the clinical and laboratory findings in an adolescent girl with status asthmaticus who developed lactic acidosis were recorded. 2) The medical records of 100 children and adolescents with status asthmaticus admitted to an intensive care unit were reviewed for laboratory evidence of lactic acidosis. 3) We also reviewed our own previous experience of status asthmaticus with respiratory failure. RESULTS Among 100 patients admitted to a pediatric intensive care unit for status asthmaticus, a single case of isolated metabolic acidosis was identified. This proved to be attributable to lactic acidosis. When records of patients with severe respiratory failure were examined, no cases of metabolic acidosis were found. CONCLUSIONS Although rare, lactic acidosis does occur in pediatric-aged patients during status asthmaticus. It is important that this complication be recognized and treated because acidosis may inhibit the effectiveness of bronchodilator therapy, produce electrolyte disturbances, and cause serious adverse effects on the patients cardiovascular system.

Selective IgM deficiency and 22q11.2 deletion syndrome

BACKGROUND The 22q11.2 deletion syndrome is a common chromosomal disorder with highly variable phenotypic expression and immunologic defects. Humoral immunity is mostly unaffected, but selective IgA deficiency occurs in up to 13% of patients. Selective IgM deficiency associated with 22q11.2 deletion has been reported in 1 patient. OBJECTIVE To describe another 2 patients with 22q11.2 deletion syndrome and IgM deficiency. METHODS Patient 1 was a 6-year-old boy with recurrent otitis media, sinopulmonary infections, wheezing, and speech delay. His serum IgM level was 18 mg/dL, and his IgA and IgG levels were normal. Antibody titers to protein and carbohydrate antigens were protective. Workup for velopharyngeal insufficiency resulted in the diagnosis of 22q11.2 deletion syndrome 3 years later. Patient 2 was a 14-year-old girl diagnosed as having 22q11.2 deletion at 9 years of age after presenting with neonatal seizures, atrial and ventricular septal defects, recurrent otitis media, mental retardation, and asthma. Her serum IgM level was 11 mg/dL, with normal IgG and IgA levels. Antibody titers to protein and carbohydrate antigens were protective. Patient 3 was a previously described 15-year-old girl with persistently draining ears, 22q11.2 deletion, and an IgM level less than 6 mg/dL. Her clinical and laboratory features are summarized. RESULTS Results of further testing on the patients, including lymphocyte enumeration, were normal. The literature is reviewed regarding decreased IgM levels in 22q11.2 deletion syndrome. CONCLUSIONS Fluorescence in situ hybridization analysis for chromosome 22q11.2 deletion should be considered in patients with selective IgM deficiency, especially if concurrent chronic otitis media, developmental delay, velopharyngeal insufficiency, or dysmorphic features are present.

Objective indicators of severity of asthma

Subjects with asthma who are intensively treated in residential care facilities frequently demonstrate marked clinical improvement in their disease, with fewer attacks and improved well being. Despite their improved status, it is known that pulmonary function test results often remain abnormal in patients with asthma. This prospective study on children with asthma receiving residential care was carried out to determine which pulmonary function parameter best reflected clinical improvement through correlation with the duration of complete freedom from wheezing. Evaluated in 42 children were spirometry values including forced vital capacity, forced expiratory volume in 1 second, peak expiratory flow rate, forced expiratory flow (between 25% and 75% of forced vital capacity), and lung volumes as reflected by residual volume/total lung capacity. Bronchial hyperreactivity as reflected by bimonthly provocative concentration causing a 20% fall in FEV1 in response to methacholine inhalation was evaluated in 18 patients. All pulmonary function test results were correlated with days since last wheezing episode. Results indicate that only peak expiratory flow rate (r = 0.91; p < 0.001), forced expiratory volume in 1 second (r = 0.69; p < 0.01), and forced expiratory flow (r = 0.62; p < 0.05) demonstrated significant correlation with the number of days since last wheezing episode. Of particular interest was the failure of bronchial hyperreactivity to improve despite intensive therapy with bronchodilators and corticosteroids. Persistence of bronchial hyperreactivity despite intensive therapy with corticosteroids suggests that in at least some children with severe asthma, bronchial hyperreactivity may be especially long-lived, may be perpetuated by inhaled beta 2 agonists, or may exist independently of airway inflammation.